内在和获得性的耐药是最终导致大多数肝癌治疗失败的原因。了解耐药产生的机制对个性化药物治疗和延长患者的生命都是至关重要的。CD133被广泛用于检测各种肿瘤干细胞的成瘤性和耐药性,但大多数研究局限于CD133阳性细胞而忽视了CD133本身的作用以及CD13与耐药形成的关系。我们发现CD133阳性细胞具有对化疗药顺铂的拮抗性，高表达CD133可延长细胞在营养缺乏状态下的存活时间，有趣的是CD133本身似乎参与细胞自噬反应。过表达CD133促进自噬，抑制CD133则明显降低自噬和自噬相关蛋白LC3的水平。自噬的活性与肿瘤耐药和药物敏感性有一定关系，肿瘤干细胞是否通过CD133介导的自噬而产生耐药尚不清楚。因此，本课题的研究目的是深入揭示CD133功能及其介导的自噬机制和膜动态变化与耐药形成的关系，从细胞群体层面研究CD133阳性细胞的生存与相邻相邻细胞的关系，为降低肝癌耐药提供新的依据。

Intrinsic or acquired chemoresistance is a major cause of treatment failure of most hepatocarcinomas. Understanding mechanisms of chemoresistance is vital for personalized treatment and survival of patients with cancer. CD133, also called prominin-1, widely used to detect tumorigenesis and chemoresistance of a variety of cancer stem cells. However, most of studies focus on CD133 positive cells rather than CD133 itself in tumor growth as well as the relationship between CD133 and chemoresistance. We find that CD133 positive cells have the ability of chemoresistance to cisplatin. Overexpression of CD133 prolongs survival period of cells in nutrition dprivation. Interestingly, CD133 appears involving autophagy by itself. Forced expression of CD133 promotes autophagy, while inhibition of CD133 by siRNA suppresses autophagy and level of LC3, one of autophagic associated proteins. Autophagic activity is believed to be responsible for chemoresistance and drug sensitivity. We are inspired by the idea that CD133-mediated autophagy may be important in chemoresistance governed by cancer stem cells. Therefore, the aim of this project is to deeply reveal mechanism of CD133-mediated autophagy and its membrane dynamic change during chemotherapy, and how this group of cells affect their neighborhood cells. The results of this projet will provide new evidence for reducing chemoresistance of hepatocarcinoma.